Project Summary/Abstract: PDX Core The PDX Core is the epicenter of the WU-PDTC as it will be responsible for the development, organization, characterization, storage, and dissemination of high quality pathogen free PDX models for research projects investigating anticancer agents, within and outside of WU-PDTC. The PDX Core builds on outstanding existing infrastructure and expertise at Washington University School of Medicine (WUSM). The Human and Mouse Linked Evaluation of Tumors (HAMLET) PDX Core at the Institute of Clinical and Translational Study (ICTS) and the Solid Tumor Tissue Bank and Registry (STTBR) led by Drs. Li and Fields, respecitvely, have a proven record of success in generating PDX models from a wide variety of cancers and in utilizing these models for drug testing. Between these programs, we have already generated over 449 PDX models across more than 12 cancer types, from the most common cancers, such as breast, lung, and colorectal, to rare cancers, such as sarcomas and lymphomas. These existing models will become part of the new WU-PDTC, where about 1000 new PDX models will be developed and added to this collection. The new PDX models will further enhance our capability to support ongoing projects and open new opportunities for research in rare cancer types. Taking advantage of the strong proteogenomic capability within the proposed WU-PDTC and WUSM, we will expand the characterization of these PDX models to include both whole exome sequencing and RNA-Seq, providing investigators with a more comprehensive picture of the mutational profiles, the molecular signatures, clonal structures, and heterogeneities of the models to help with cancer sub-typing and target selection. Besides research projects at WU-PDTC, PDX models in the PDX Core collection will also be shared with other PDTCs and made broadly available to authorized non-network investigators. Furthermore, the PDX Core will study new approahes to improve the take rate, fidelity, and characterization of PDX models. The large patient base and exceptionally strong institutional backing, including matching funds, will additionally ensure that these goals are achievable.